We have continued our search to identify the key paracrine factors regulating endochondral bone formation in the growth plate. In the past year, we focused on four extracellular signaling molecules, retinoic acid, C-type natriuretic peptide, bone morphogenetic protein-2 and Ca2+, examining their effects on growth plate chondrocyte proliferation, differentiation, and cartilage matrix production. We have also explored the mechanisms governing spatial organization of growth plate chondrocytes. Our findings suggest that this spatial organization is not dependent on signals from the surrounding bone but rather on a growth plate-orienting factor that originates in the resting zone of the growth plate cartilage itself. Ongoing studies examine the mechanisms by which estrogen causes epiphyseal fusion, the identity of the growth plate stem cell, and the relationships between skeletal growth and osteoporosis. - bone, cartilage, growth, plate, chondrocytes, stature, osteoporosis